{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T22:10:49Z","timestamp":1698531049268},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,2,3]],"date-time":"2009-02-03T00:00:00Z","timestamp":1233619200000},"content-version":"vor","delay-in-days":4296,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1997,5]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>We have investigated the role of phosphatases in modulating contractile responses to electrical field stimulation (EFS), methacholine, substance P and capsaicin in guinea\u2010pig isolated main bronchus by use of the phosphatase 1 and 2A inhibitor okadaic acid.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Non\u2010adrenergic non\u2010cholinergic (eNANC) contractile responses were elicited by EFS (3 Hz, 20 s, 0.5 ms max. voltage) in the guinea\u2010pig isolated main bronchus in the presence of the non\u2010selective muscarinic antagonist, atropine (1 \u03bc<jats:sc>M<\/jats:sc>), the non\u2010selective \u03b2\u2010adrenoceptor antagonist, propranolol (1 \u03bc<jats:sc>M<\/jats:sc>), the neutral endopeptidase inhibitor thiorphan (10 \u03bc<jats:sc>M<\/jats:sc>) and the cyclo\u2010oxygenase inhibitor, indomethacin (5 \u03bc<jats:sc>M<\/jats:sc>). Okadaic acid significantly attenuated eNANC contractile responses (% inhibition) elicited by EFS (0.01 \u03bc<jats:sc>M<\/jats:sc>, 15.2\u00b126.9%; 0.03 \u03bc<jats:sc>M<\/jats:sc>, 30.4\u00b113.9%; 0.01 \u03bc<jats:sc>M<\/jats:sc>, 39.8\u00b15.1%; 0.3 \u03bc<jats:sc>M<\/jats:sc>, 59.5\u00b18.7%; 1 \u03bc<jats:sc>M<\/jats:sc> 77.8\u00b17.8%; <jats:italic>P<\/jats:italic>&lt;0.05, <jats:italic>n<\/jats:italic>=4). In contrast, the inactive analogue 1\u2010Nor okadaone (0.3 \u03bc<jats:sc>M<\/jats:sc>) failed to attenuate significantly eNANC contractile responses (% inhibition elicited by 1\u2010Nor okadaone, \u22121.25\u00b18.5% vs dimethylsulphoxide (DMSO), \u221213.5\u00b121.5%; <jats:italic>P<\/jats:italic>&gt;0.05, <jats:italic>n<\/jats:italic>=4).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Cholinergic contractile responses were elicited by EFS (1\u201330 Hz, 10 s, 0.5 ms max. voltage) in guinea\u2010pig isolated bronchus in the presence of the nitric oxide synthase inhibitor, N<jats:sup>\u03c9<\/jats:sup>\u2010nitro\u2010<jats:sc>L<\/jats:sc>\u2010arginine methyl ester (<jats:sc>L<\/jats:sc>\u2010NAME, 30 \u03bc<jats:sc>M<\/jats:sc>). Okadaic acid failed to attenuate significantly the contractile (% methacholine E<jats:sub>max<\/jats:sub>) response elicited by EFS at all frequencies tested compared with the control (1 Hz, control, 22\u00b17.9% vs okadaic acid, 18\u00b17.7%; 3 Hz, control, 26\u00b16.9% vs okadaic acid, 27\u00b19.1%; 10 Hz, control, 36\u00b17.6% vs okadaic acid, 33\u00b18.9%; 30 Hz, control, 50\u00b17.6% vs okadaic acid, 42\u00b114%; <jats:italic>P<\/jats:italic>&gt;0.05, <jats:italic>n<\/jats:italic>=4).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Okadaic acid (0.3 \u03bc<jats:sc>M<\/jats:sc>) failed to alter significantly the contractile potency (pD<jats:sub>2<\/jats:sub>) to capsaicin (okadaic acid, 9.0\u00b10.5, vs DMSO, 9.2\u00b10.4; <jats:italic>P<\/jats:italic>&gt;0.05 <jats:italic>n<\/jats:italic>=6), substance P (okadaic acid, 7.6\u00b10.3 vs DMSO, 8.2\u00b10.2; <jats:italic>P<\/jats:italic>&gt;0.05 <jats:italic>n<\/jats:italic>=7) or methacholine (okadaic acid, 6.4\u00b10.2 vs DMSO, 6.4\u00b10.3; <jats:italic>P<\/jats:italic>&gt;0.05 <jats:italic>n<\/jats:italic>=4).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Okadaic acid (0.01\u20131 \u03bc<jats:sc>M<\/jats:sc>) did not appear to reverse substance P\u2010induced tone. The maximal relaxant response (% reversal of substance P\u2010induced tone) mediated by okadaic acid (1 \u03bc<jats:sc>M<\/jats:sc>) was 33\u00b111.7% (<jats:italic>n<\/jats:italic>=4), this was not significantly different from the DMSO (0.8%) or a time\u2010dependent fall in tone of 34.3\u00b123.1% (<jats:italic>n<\/jats:italic>=4) and 33\u00b115.8% (<jats:italic>n<\/jats:italic>=4), respectively. Okadaic acid (0.3 \u03bc<jats:sc>M<\/jats:sc>) failed to augment isoprenaline\u2010induced relaxation repsonses in substance P contracted bronchus (okadaic acid, 6.5\u00b10.4 vs DMSO, 5.9\u00b10.3; <jats:italic>P<\/jats:italic>&gt;0.05, <jats:italic>n<\/jats:italic>=9).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results indicate that protein phosphatases appear to regulate the release of sensory neuropeptides from airway sensory nerves in response to electrical field stimulation.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1997) <jats:bold>121<\/jats:bold>, 181\u2013186; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0701114\">10.1038\/sj.bjp.0701114<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0701114","type":"journal-article","created":{"date-parts":[[2006,8,25]],"date-time":"2006-08-25T17:09:36Z","timestamp":1156525776000},"page":"181-186","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The effect of okadaic acid on non\u2010adrenergic non\u2010cholinergic contraction in guinea\u2010pig isolated bronchus"],"prefix":"10.1111","volume":"121","author":[{"given":"S","family":"Harrison","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D","family":"Spina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C P","family":"Page","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.5.1803"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1990.tb12080.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1992.tb09027.x"},{"key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1183\/09031936.93.05101201","article-title":"Modulation by theophylline and enprofylline of the excitatory non\u2010cholinergic transmission on guinea\u2010pig bronchi","volume":"5","author":"Barlinski J.","year":"1992","journal-title":"Eur. Respir. J."},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00172684"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(92)90492-M"},{"key":"e_1_2_6_8_1","doi-asserted-by":"crossref","first-page":"C387","DOI":"10.1152\/ajpcell.1991.261.2.C387","article-title":"Regulation of Ca(2+)\u2010activated K+ channels by protein kinase A and phosphatase inhibitors","volume":"261","author":"Carl A.","year":"1991","journal-title":"Am. J. Physiol."},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(93)90315-7"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0968-0004(90)90192-E"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(89)90399-3"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1989.tb12611.x"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8430330"},{"key":"e_1_2_6_14_1","doi-asserted-by":"crossref","first-page":"6013","DOI":"10.1523\/JNEUROSCI.14-10-06013.1994","article-title":"Activity\u2010dependent enhancement of synaptic transmission in hippocampal slices treated with the phosphatase inhibitor calyculin A","volume":"14","author":"Herron C.E.","year":"1994","journal-title":"J. Neurosci."},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00582504"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(94)90308-5"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1989.tb12672.x"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(89)92189-X"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1996.66051924.x"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1989.tb12633.x"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/341152a0"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01871217"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(88)90282-8"},{"key":"e_1_2_6_24_1","first-page":"L449","article-title":"Release of tachykinins by histamine, methacholine, PAF, LTD4 and substance P from guinea\u2010pig lungs","volume":"261","author":"Martins M.A.","year":"1991","journal-title":"Am. J. Physiol."},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1006\/pulp.1993.1037"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(94)90556-8"},{"key":"e_1_2_6_27_1","first-page":"535","article-title":"Biochemical and electrophysiological mechanisms of the positive inotropic effect of calyculin A, a protein phosphatase inhibitor","volume":"271","author":"Neumann J.","year":"1994","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/11.10.1837"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00580954"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)00397-N"},{"key":"e_1_2_6_31_1","first-page":"1167","article-title":"Calcium\u2010independent phosphorylation of smooth muscle myosin light chain by okadaic acid isolated from black sponge (Halichondria okadai)","volume":"243","author":"Ozaki H.","year":"1987","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.94.07020306"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.11-06-01627.1991"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.13.2.7626289"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1995.269.3.C725"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)37100-4"},{"key":"e_1_2_6_37_1","first-page":"A484","article-title":"The release of substance P\u2010like immunoreactivity from guinea\u2010pig isolated bronchus","volume":"153","author":"Shah S.","year":"1996","journal-title":"Am. J. Respir. Crit. Care. Med."},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb15074.x"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/neu.480220806"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(87)81247-4"},{"key":"e_1_2_6_41_1","first-page":"811","article-title":"Inhibition of neurally mediated nonadrenergic noncholinergic contractions of guinea\u2010pig bronchus by isozyme\u2010selective phosphodiesterase inhibitors","volume":"271","author":"Undem B.J.","year":"1994","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_6_42_1","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1152\/jn.1993.69.3.717","article-title":"Facilitation and delayed release at about 0 degree C at the frog neuromuscular junction: effects of calcium chelators, calcium transport inhibitors, and okadaic acid","volume":"69","author":"Van Der Kloot W.","year":"1993","journal-title":"J. Neurophysiol."},{"key":"e_1_2_6_43_1","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1152\/jappl.1993.74.3.1195","article-title":"\u03b2\u2010Adrenoceptor agonists inhibit NANC neural bronchoconstrictor responses in vitro","volume":"74","author":"Verleden G.M.","year":"1993","journal-title":"J. Appl. Physiol."},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(95)11576-I"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1995.sp020688"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0701114","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0701114","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0701114","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T05:36:49Z","timestamp":1698385009000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0701114"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,5]]},"references-count":44,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1997,5]]}},"alternative-id":["10.1038\/sj.bjp.0701114"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0701114","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,5]]},"assertion":[{"value":"2009-02-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}